Safety and Efficacy of Mesenchymal Stem Cell Therapy in Multiple System Atrophy: Systematic Review

To systematically evaluate the efficacy and safety of mesenchymal stem cell (MSC) therapy for patients with Multiple System Atrophy (MSA) by synthesising available clinical trial evidence and clarifying signals of disease modification.

MSA is a rapidly progressive and fatal neurodegenerative disorder for which no disease-modifying therapies exist. MSC therapy has emerged as a potential treatment, with mechanisms centered on neuroprotection and clinical benefit through anti-inflammatory and trophic effects rather than direct cell replacement.

We systematically searched PubMed, Scopus, the Cochrane Library, and Web of Science for studies on mesenchymal stem cell (MSC) therapy in adults with probable or confirmed multiple system atrophy (MSA). Eligible studies included single-arm trials or comparisons with placebo or usual care. The primary outcome was safety and tolerability, assessed by the type and severity of adverse events. Secondary outcomes included the rate of disease progression measured by UMSARS total, Part I, and Part II scores.

A total of 123 participants from seven studies were included. MSCs were administered through multiple routes, and adverse events occurred in 65-70% of participants but were mostly mild and transient. No serious MSC-related toxicity was reported. Several studies suggested slower disease progression following MSC therapy. For example, in Singer et al (2019), patients receiving high-dose MSCs showed a markedly lower rate of UMSARS total score progression compared with a matched historical control group (0.40 ± 0.59 vs 1.44 ± 1.42 points/month, p = 0.004), suggesting a possible dose-dependent effect. However, treatment effects varied across studies depending on dose, administration route, and disease stage.

MSC therapy shows potential for disease modification in MSA by slowing neurological deterioration. The treatment was well tolerated, supporting the need for larger, definitive trials with standardised protocols and longer follow-up to confirm clinical benefit.